Study of Valproic Acid Liposomes for Delivery into the Brain Through an Intranasal Route

Abstract

Intranasal drug transport through the olfactory route to the brain is an effective drug route for increased absorption and bioavailability of the drug. The objective of this study was to increase the penetration of valproic acid as an anticonvulsant into a delivery system comprising liposomes. Valproic acid liposomes were prepared by a thin-layer hydration technique using soybean phosphatidylcholine and cholesterol as the main ingredients. The formulations were evaluated for diameter size, entrapment efficiency (EE), zeta potential, polydispersity index, and morphology. Ex vivo permeation using sheep nasal mucosa and in vivo efficacy were assessed by performing a pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison with pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 210 nm with a low polydispersity index (<0.5). The EE of optimized liposomes was between 60% and 85%, increasing the concentration of phosphatidylcholine added to the formula. Transmission electron microscopy observations (40,000´) showed that valproic acid liposomes have a spherical molecular shape and a particle size of below 250 nm. The ex vivo and in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, Formula 4 (F4) showed greater uptake of valproic acid into the brain than plasma. The high brain targeting efficiency index for F4 indicated the preferential transport of the drug to the brain. The study demonstrated the successful formulation of surface-modified valproic acid liposomes for nasal delivery with brain targeting potential. Funding Information: Mahdi jufri received Research Grant of the University’s Base Research Program from Directorate of Research and Community Engagement University of Indonesia, Indonesia. Declaration of Interests: There was no conflict of interest to declare. Animal Welfare: The ethics committee approved the protocol (KET1065/UN2.F1/ETIK/PPM.00.02.2019).